Squats.....a continuation

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  1. Squats.....a continuation

    Ok, a previous thread brought this up in heated debate, and I found this point very interesting: what role do squats really play in lean mass gains and training in general? Let me preface this by saying two things:

    1. I don't exactly have a concrete opinion either way. If I did I wouldn't be asking for a discussion, lol. I have always been a believer that squats should be done in nearly any resistance training program, and do still believe this, but rather want to clarify why and what actual tangible effects are from incorporating this exericse in training vs. other variables in the training equation when squats are added.

    2. If we get into a pissing match or flaming, I will close the thread immediately and delete it. Everyone has a different opinion and I respect that, but please make yours logically based and at least know that if you put a statement of fact out there it may be challenged.

    Now, I'm starting HST training and found these statements by Bryan Haycock very interesting considering what I was reading in another thread:

    From the HST FAQ Forum, click here

    The problem with squats is that they are a very complicated exercise...By complicated I don't just mean the movement itself, but the number of variables that come into it when you are dealing with all sorts of people with all sorts of abilities and tolerances.

    I would say about 85% of the bodybuilding population don't perform squats properly. Why so many? Because they are unaware that they are not doing them correctly. They think they’re doing squats, when in reality they are doing partials, using a lot of low back. Balance is usually over the balls of the feet and the knees come in until they nearly touch. Power lifters and Olympic lifters are much better at this because they are “trained? to squat properly from the very beginning. Olympic lifters, in my opinion, have the most beautiful squatting technique I have seen among all lifters.

    There is also the problem of ego. Like bench, everybody seems to think you aren’t cool unless you squat a ton of weight. This puts undue pressure on people to increase the weight beyond their capacity. As a result, their execution of the exercise deteriorates even further.

    Finally, one other variable referring specifically to muscle growth is exercise tolerance. People often don’t realize how agonizing and painful a true set of squats can be. I mean, anybody can burn the crap out of their biceps doing concentration curls, or even their chest doing crossovers or pec-deck. But put several hundred pounds on their back and tell them to keep going until the pain is so bad they think they will surely be crushed, die, or both and you are talking about something most people have never experienced…even most casual lifters. Most people simply rack the weight before they really stress the legs. As a result, their squatting weight will be significantly less than it is for their other leg exercises. In other words, they are unable or unwilling (consciously or not) to perform squats in the way necessary to illicit a significant growth stimulus.

    So take this group of bad squaters, give them squat advice, and it is anybody’s guess what kind of results they will have. Simply because they don't perform them properly. As a result of that, there will crop up dozens of squatting routines all promising huge gains. Not only that, but squats do not cause whole body growth. They only have the potential to cause growth in those muscle groups directly involved in the squatting movement. However, because squats involve at least half of the body, you can increase overall bodyweight as a result of so much of the body’s musculature being stimulated to grow. Despite Kraemer’s claims that the miniscule spikes in Test and GH as a result of squatting without resting too much in-between sets is responsible for muscle growth, it isn’t entirely true. Otherwise, if these minute spikes in Test and GH had any significant physiological effect, squatting would put hair on your chest. Ok, I’m being a little sarcastic but you get my point.

    The anabolic potential of any given squatting routine, be it 20 rep, Breathing squats, Oxford method, Straight sets, Super Slow, HIT, GVT, EDT, or HST, depends on the individual’s level of conditioning in the legs when they begin a squatting routine.

    For someone who has been frustrated with their legs and/or squats and hasn’t been squatting properly or diligently, anyone of the above mentioned methods would lead to some size gains… Then that person runs out and tells everybody that they have found the answer to getting legs like Tom Platz. So depending on who’s asking, sure, small increments, or even no increments will work for a lot of people, just as long as they are consistent, and are able to push themselves to the point that they are really causing some trauma to the tissue.

    For those who are healthy, squat well, squat relatively frequently, and are somewhat already developed, I recommend HST as indicated (accept for negatives). For those who struggle with squats for one reason or another, simply add leg extensions, and/or leg press, using the HST method.

    So, both SD and the bigger increments are going to be necessary for people who have been already training legs properly and are already bigger than they would be without training much. Other people will get by with less simply because they haven’t been training all that well to begin with.

    - Bryan

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  3. I always get in a vicious 3 month cycle with squats. I'll start at a weight I can control and do with good form then I'll gradually increase the weight every week. I won't even realize I'm cheating. Eventually I get much higher weight, but at that point I'll ask someone how far I'm going down, and it turns out I'm doing half squats. Then I'll go back down to a low weight I can control and use good form and do it all over again, telling myself I'm not going to cheat myself anymore.

  4. Quote Originally Posted by RobInKuwait
    I always get in a vicious 3 month cycle with squats. I'll start at a weight I can control and do with good form then I'll gradually increase the weight every week. I won't even realize I'm cheating. Eventually I get much higher weight, but at that point I'll ask someone how far I'm going down, and it turns out I'm doing half squats. Then I'll go back down to a low weight I can control and use good form and do it all over again, telling myself I'm not going to cheat myself anymore.
    I do the same thing, I think it happens to most of us. With this HST I just started I have to watch out to keep perfect form, and luckily the first two weeks or so will let me focus on that. It's just seems easy to slightly alter form for weight, even if it's barely noticeable each workout...after about a month or two you really can notice a difference. I see guys at the gym doing it all them time unfortunately (including myself). Someuimes I'll increase tempo throughout the positive part of the exercise, which I'm OK with, but when you notice you're not going low enough or arching too much with the back you know it's time to refocus on form.

  5. I agree, I think the best way to keep good form is having a training partner. Normally I'm not a big fan of having training partners, but for squats I think its a huge help. They can check your form and make sure youre not cheating yourself, while at the same time making sure you don't die when you hit failure with hundreds of pounds of metal sitting on your back

    Quote Originally Posted by jweave23
    I do the same thing, I think it happens to most of us. With this HST I just started I have to watch out to keep perfect form, and luckily the first two weeks or so will let me focus on that. It's just seems easy to slightly alter form for weight, even if it's barely noticeable each workout...after about a month or two you really can notice a difference. I see guys at the gym doing it all them time unfortunately (including myself). Sometimes I'll increase tempo throughout the positive part of the exercise, which I'm OK with, but when you notice you're not going low enough or arching too much with the back you know it's time to refocus on form.

  6. And you can throw tibits up all day and I can counter all day with others that show a contrary opinion. I KNOW how it works in the gym with real trainees though. One thing you seem to keep missing is believing I and others are stating you only need to squat and your upper body will grow without direct work. What is being stated is WHEN squatting the body will will respond MUCH better to the direct work done.

    Human Growth Hormone
    by Ron Kennedy, M.D., Santa Rosa, California
    The full story on aging is as yet incompletely known. Why do we age? What changes us, and what can we do about it to halt, reverse, or at least slow down this process? One factor which is important in the aging process, is the slowing down of the hormonal system, particularly the adrenal glands and the thyroid gland. A program to slow the aging process must take into consideration the function of these two glands or be woefully inadequate. Thyroid extract and DHEA have become mainstays in the treatment of premature aging. Human growth hormone (abbreviated HGH) is produced in the pituitary gland, a tiny gland at the base of the brain which regulates the endocrine glands. The pituitary is the master gland which regulates the entire hormone system. In fact, 40% of the anterior pituitary cells are "somatocytes," cells which make HGH. Based on the number of cells devoted to the job, nature seems to think the production of HGH is critically important.
    The Biochemistry of HGH
    The biochemistry of HGH is complex. It seems that we all have plenty of HGH, but as we age it is prevented from being released from the pituitary by deficiency of HGH releasing hormone (HGHRH) which is made in the hypothalamus of the brain and by a substance called HGHP, a peptide of seven small amino acids. One day it may be possible to supplement with one or both of these two substances and cause the release of your own HGH; however as yet these are not commercially available.
    For people who want to get the full benefit of HGH, it is necessary to raise plasma levels to those enjoyed by the average person in his or her 20s. We need 30-50% of the amount children have and very few adults produce and release this much on his/her own.
    Some of the effect of HGH are immediate: increased energy, ability to concentrate, interest and ability in sex; others take a few months to a year to show up: increased aerobic capacity and strength, thickening of hair, tightening of wrinkles and loose skin, decrease in visceral fat; and one takes two years: strengthening of osteoporotic bones.
    I prefer to treat illnesses at the most fundamental level and for many of the ailments of "old age" the most fundamental cause is HGH deficiency. The only treatment which fully reverses HGH deficiency is HGH replacement therapy.

    HGH is a powerful rejuvenating agent. Unfortunately, it also is super-expensive. Many hormones are exactly the same in animals and humans, but human growth hormone is different from that produced in the pituitary gland of any other animal. Until recent years it had to be harvested in minute quantities from human pituitaries.
    In the 1980s, it became possible to synthesize HGH using recombinant DNA techniques, coaxing bacteria to do the job by inserting the proper human gene into their genome. The average cost of one year of therapy is $10,000 which makes this a rich person's therapy. The price may come down in the future, but it will never be cheap.
    In addition, HGH is stringently controlled. Because there is a potential for abuse, the legitimate need for HGH must be thoroughly documented. However, most people over age fifty, and many younger than that, can be shown to be in need of HGH for optimal health. In the ideal world, everyone in need of HGH would receive it. Because of economic and other considerations, only a fortunate few will receive it.
    Anaerobic Exercise
    Now, let us talk about the most powerful way possible to increase growth hormone release: exercise. Vigorous, sustained, anaerobic exercise causes the release of growth hormone, as every serious body builder knows well.
    There is one way to block the release of growth hormone, even in the presence of this type of exercise, and that is carbohydrate intake. For maximal effect, body builders consume pure protein, no carbohydrates, and pump iron to exhaustion. (I am not suggesting you do that, only making a point.)
    To get the best HGH release, use of the largest muscles in the body is best, namely the lower extremities. A body-builder favorite is to place a heavy barbell on the shoulders and do repeated squats. They do not reach for the sport drink after that because the infusion of carbs wipes out the HGH response.
    If you are doing "aerobics," and you want to get into the anaerobic range to reap the benefits of HGH release, it is necessary to press yourself into the painful zone, which is how it feels to be running, bicycling, etc. in an anaerobic condition. The maximum workout time is fifteen to thirty minutes. (This is not something you should try until you have received clearance from your doctor.) After that, if you have done it correctly, you cannot continue, due to exhaustion. Recovery should take five minutes, and at that time your heart should have returned to its resting rate. If it does not, see your doctor.
    Also, if you do not feel absolutely wonderful thirty minutes later, see your doctor about possible adrenal weakness. Of course, your doctor must also be aware of these things, and therefore I recommend that you choose your doctor carefully. Not all docs are informed about exercise hormone physiology, since there is no synthetic drug to prescribe for it.
    Of course, you must get your doctor's okay before you do these types of strenuous exercises pumping iron and "anaerobic aerobics." You must be certain that your heart can take it, and you must begin slowly and build up. I strongly recommend that you find a trainer to help get you started.
    Testosterone Anyone?
    You ever see those guys that are built like kites? Big huge lat spreads with backs the size of the Rockies that then taper down to a tiny waist with legs that look like the string on the kite? These guys look ridiculous, but they are all over the gyms. I recall a guy that always wore tank tops and jogging pants to the gym. From up top I would say he could have easily weighed 240lbs at 5'9. We were talking one day and he eeked out, "I weigh 205!" "205", I shouted, "you don't do any legs at all, do you?" We know his answer.
    Did you know that doing squats on a big body part like quads flushes your body with added testosterone and growth hormone (1)? You can suddenly start to really pack on pounds by simply adding a compound movement like squats into your program.
    Working out your legs hurts. You know it, you've got to suck it up and plunge right in. If you want Priest or Cutler like legs you've got to train them heavy and hard with a decent amount of volume to stimulate all of those motor units. Don't use the "but I don't do steroids" excuse. As of today (April 23rd, 2003) I've been clean for about 6 years. I've got 28-inch thighs on a 5'8 frame. How do I know this is all natural growth? I was scared of doing legs 6 years ago. I never got above 185lbs until I started cranking in some SERIOUS legwork, consistently. As soon as I started I couldn't stop growing!

    By: Louie Simmons
    Overcoming Plateaus
    Your squat is going nowhere. No matter what you do it won’t increase. What can you do? Well first, let’s find the real problem. It can be several things: form, exercise selection, volume, and the development of special strength, i.e., starting, accelerating, eccentric, concentric, reversal, static, and of course absolute.
    First, let’s talk about form, Box squatting is a must. Use a box that is slightly below parallel. Sit fully on the box, keeping all muscles tight, most importantly the abs and the obliques. By releasing only the hip muscles you are going from a relaxed state to a dynamic phase. This is one of the best methods of developing absolute strength as well as explosive strength. Lowering the bar produces a great amount of kinetic energy, which is stored in the body, resulting in reversal strength.
    For box squatting, the form is the same as regular squatting. Before descending, the glutes must be pushed out to the rear. Because you are going to squat to the rear and not down, this sets up the body for a stretch reflex. Next, push the knees out to the sides. This accomplishes two things: It places much of the stress, or work, on the hips, and it will greatly increase your leverage in the bottom of the squat. By pushing the knees out, you are at least attempting to keep the knee joint in line with the hip joint. In theory, if you can stand up with 1000 pounds while your shoulder, hip, knee, and ankle joints are in line, you could squat to parallel with the same weight if the above joints are kept in line. That is why it is so important to super-arch the back, by keeping the chest up, while in the bottom of a squat.
    If you correctly push the glutes out first on the descent, then the head will move last. On the ascending phase, the reverse is true. The head must come up first by pushing the head into the traps. It is then natural for the hips and glutes to follow. Also, never push down with the feet when squatting. You must push out to the sides on the eccentric and concentric phases. That’s why we recommend Chuck Taylor shoes. The feet can be pushed out to the sides without the feet rolling over. When sitting on the box, it is possible, and desirable, for the shins to be past perpendicular. This places all the work on the vital squat muscles. This is impossible with regular squatting.
    Train on a box with 50-60% of your best contest squat. A 500 pound squatter would start at 250 and jump 10 pounds a week for 6 weeks. Now the weight is 300 pounds. On week 7 drop back to 250(50%) and a new wave. This is done for 10 sets of 2 reps for 4 weeks. Then drop to 8 sets. This will keep the bar volume relatively the same. The volume will change dramatically when you start the wave again, adding 3 or 4 special exercises that have not been used for a period of time.
    The combination of changing special exercises and using short rest periods (about 40 seconds between sets) has proven to be most effective for producing growth hormone. The short rest will cause lactic acid to build up.
    When you fight through this discomfort, you will produce the most growth hormone. Also, when you use maximal weights in the same exercise for more than 3 weeks, growth hormone production stops! Wusef Omar, a colleague of the renowned Tudor Bompa, with the help of top exercise physiologists, validated this at York University in Toronto.

    Manipulating Hormone ReleaseNaturally with Resistance Training
    By Patrick Gamboa B.S.Resistance training is the best natural stimulus for muscular growth. Many weight training programs have been developed over the years in an attempt to modify and manipulate this natural process, each with varying degrees of success. The truth is, the success of a program is often determined by its ability to elicit a specific hormonal response, and little else.Hormones circulating during and after workouts directly affect muscle adaptation. Unfortunately, this is one of the most misunderstood aspects of resistance training. If we as trainers understood the natural anabolic activity in our clients resulting from specific styles of strength training, we could surely design more effective programs enabling our clients to recover faster, adapt and grow more effectively. Let's look at the factors of muscle fiber recruitment, and manipulating serum testosterone and growth hormone levels through resistance training.The average beginning trainee knows that high repetitions (15 repetitions or more) is best for muscular endurance, and is not conducive to gaining muscular mass. The light weight used in high repetition work is not enough to innervate the higher threshold motor units in a muscle. The key is that only muscle fibers activated by the resistance training will respond to increased levels of anabolic hormones. When heavier weights (lower reps) are used in resistance training, more muscle fibers are recruited. The more muscle fibers recruited for an exercise, the greater the extent of remodeling in the entire muscle.There is another reason that light weight and high repetitions are not optimal for stimulating muscular hypertrophy. The majority of the work done in high repetition sets is accomplished by slow-twitch Type I muscle fibers. Type I muscle fibers have a limited ability to hypertrophy. Type IIB fibers are activated when more force is required, and thus have the greatest potential for growth. Heavier weights accomplish more complete activation of the type 11B muscle fibers.According to the size principle, motor units are recruited in order according to their recruitment thresholds and firing rates. Since most muscles contain a range of Type I and Type II fibers, force production can be very low or very high. Therefore, to get to a high-threshold motor unit, all of the motor units below it must be sequentially recruited. Heavy resistance training recruits these high threshold motor units, therefore all the units below it can undergo hormonal adaptations to the stress of the heavy loads.An increase in serum testosterone levels is one result of heavy resistance training. Since testosterone is the primary hormone that interacts with skeletal muscle tissue, it has both direct and indirect effects on muscle tissue. Resistance training utilizing large muscle groups of the lower body (squats, deadlifts) can increase serum testosterone concentrations more than other types of exercises. Using a resistance of 85%-95% of one-rep maximum will also increase testosterone levels more than other resistance loads. Many aspiring novices will attempt to lift near 1 RM loads for one or two repetitions in the hopes of gaining muscle size. Although heavy resistance does innervate high threshold motor units, serum testosterone levels are increased through moderate to high volume of exercises. This is achieved through multiple sets, exercises, and a moderate repetition range (around 10 repetitions), with short rest intervals (between 30 seconds to 1 minute).For gains in muscular size, smaller motor units need to be recruited first in each set of exercise. As the set progresses in intensity, larger units will then be recruited. If the low threshold motor units are inhibited to recruit the high threshold motor units for explosive movements (as in powerlifting), the low threshold units that are not activated will not undergo hormonal adaptations. This is because of the size principle of muscle fiber recruitment. Since motor units are recruited in an orderly fashion (from low threshold to high) and can span a range of muscle fiber types (Type I and Type II), then a moderate range of repetitions must be used to recruit the entire spectrum of fibers. This recruitment pattern allows the full spectrum of fibers to adapt to the training by increasing sensitivity to circulating anabolic hormones.After a muscle has been subjected to intense stress through maximal force contractions over a moderate repetition range, hormones begin the growth process and muscle remodeling. Growth hormone plays a vital role in adapting to the stress of resistance training. Growth hormone levels can be increased through resistance training through high intensity (10 repetitions coupled with heavy resistance) with three sets of each exercise (high total workload) and short, one minute rest periods. Once the levels are elevated, a cascade of events occur; decreased glucose utilization, increased amino acid transport across cell membranes, increased protein synthesis, increased utilization of fatty acids, increased lipolysis (fat breakdown), enhanced immune functions, and a promotion of compensatory renal hypertrophy.An understanding of natural anabolic activity, which occurs in your clients’ bodies, is essential to muscular adaptation, successful recovery, training progression, and ultimately muscular gains. High repetition resistance training (15 repetitions or more) does not innervate high threshold motor units and therefore limits the potential for Type IIB muscle fiber hypertrophy. Powerlifting, which does not allow for sufficient time to activate all motor units in an orderly fashion, diminishes the hormonal adaptations of the entire span of muscle fibers in any given motor unit. Only resistance training that is high in intensity, utilizing 8-10 repetitions, heavy resistance and a maximum of one minute rest between sets will maximize serum testosterone and growth hormone levels, thus allowing for successful recovery, adaptation, and muscular growth.Patrick Gamboa B.S.

  7. Lmao!!!!
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  8. Bobo, does this mean you think Loius doesn't know ****?

    Not putting words in your mouth, just wondering-lol.

    Iron Addict

  9. "I KNOW how it works in the gym with real trainees though"

    That part is funny.
    For answers to board issues, read the Suggestion and News forum at the bottom of the main page.

  10. So now we're back to GH causing this overall growth:

    Ok then,

    Recombinant Growth Hormone and the Athlete
    by Nandi

    In last month’s issue of Mind and Muscle (M&M #14) we looked at how growth hormone has been used in a number of trials to successfully induce weight loss in obese humans.

    In order to better understand how GH affects this weight loss we also discussed in some detail how growth hormone and fat cells interact with one another. In this review of the existing literature, I would like to look at another growing use of recombinant GH: its use to increase athletic performance and increase muscle mass. There are much less data to guide us here than was available in our discussion of GH treatment of obesity. Further, the scientific literature contrasts starkly with the vast number of anecdotal reports of dramatic improvement in athletic performance and muscle mass seen with GH use. The scientific literature paints a rather bleak picture of recombinant GH as an ergogenic aid.

    The positive results of some of the obesity trials discussed in Mind & Muscle #14 do suggest that GH might be beneficial to athletes and bodybuilders for weight loss while maintaining lean body mass. In fact, the studies in which recombinant GH has been administered to athletes and healthy young adults have yielded mixed results in terms of changes in strength and body composition, with the data often being difficult to interpret. This will be evident upon looking in detail at the research. For example, Yarasheski et al (1) looked at the effect of 14 days of recombinant GH administration (40 mcg/kg/day) on muscle protein synthesis rates in experienced weight lifters. The authors concluded that short-term GH administration neither increased the fractional rate of skeletal muscle protein synthesis nor did it reduce the rate of whole body protein breakdown despite significantly elevated levels of circulating IGF-1. This is in contrast to research that has shown that GH administration in normal, healthy humans in the postabsorptive state increases net muscle amino acid balance during the period of GH infusion (2). This anabolic effect is evidently short lived, since as mentioned, long-term studies show no increase in muscle mass. Note that in the study by Yarasheski et al protein synthesis/breakdown rates were measured several hours after the last GH injection, not during an infusion as in (2). Nevertheless, IGF-1 levels were still elevated 2 fold above baseline when Yarasheski et al collected their data.

    As an aside, in another interesting study (3) that looked at the short-term infusion of a combination of GH and insulin, GH once again appeared to increase protein synthesis, but it also blunted the normal antiproteolytic effects of insulin.

    Yarasheski et al (4) conducted another study in which GH was administered to healthy young men in conjunction with a resistance training program. The authors measured a number of parameters: change in body composition; muscle strength improvement; whole body protein turnover; and fractional muscle protein synthesis rate. Compared to placebo, the GH treated group showed a significantly larger increase in fat free mass. However, due to the rapid gain in this mass and the rapid loss after treatment ended, the authors attributed this gain primarily to water retention. There was no difference in strength gains between the GH and placebo treated groups. The GH treated group showed an increase in whole body protein synthesis but no change in fractional skeletal muscle synthesis rate. From this, and the lack of strength gains and muscle circumference, the authors deduce that the net protein accretion was not in the form of skeletal muscle.

    Deyssig et al (5) conducted a similar study in trained power athletes. One group was given rhGH at 0.09 U/kgBW day while another was given placebo. Both groups participated in a resistance training program for six weeks. At the end of the study period changes in strength and body composition were measured in both groups. Again there was no difference between the two groups in the parameters measured. The authors concluded that GH treatment had no effect on strength or body composition in highly trained strength athletes.

    Crist et al (6) examined the effects of six weeks of rhGH administration (30 – 50 mcg/kg, 3 days per week) in a group of young, highly conditioned (resistance and aerobic trained) men and women. FFM increased more (2.7 kg) and body fat decreased more (1.5 kg) during the GH treatment period than during the six-week placebo treatment period. It is unclear however whether the increase in FFM was due to any accumulation of skeletal muscle (contractile) protein. The study did demonstrate a greater fat loss during the GH period. This is consistent with some of the research presented last issue of M&M showing that GH treatment is capable of promoting fat loss.

    In bodybuilders wishing to lower their body fat levels to what is humanly feasible, GH may be a viable option if one is willing to accept the possibility of some unhealthful side effects. In competitive endurance or strength athletes, as opposed to bodybuilders, the detrimental effects of GH use on performance may argue against its use. In a review of the topic (7) Rennie cites recent research conducted at the Danish Institute of Sports Medicine where GH administration to trained athletes actually impaired their performance (8). In these studies healthy endurance trained athletes were unable to complete accustomed cycling tasks after administration of exogenous hGH. The authors suggest that this could be a result of an observed increase in plasma lactate in the GH group compared to placebo. The significantly elevated lactate could result from the inhibition of the enzyme pyruvate dehydrogenase (PDH) by high levels of fatty acids released during GH-stimulated lipolysis. With PDH thus inhibited, pyruvate, produced from the glycolysis of glucose, is unable to enter the mitochondrial citric acid cycle and accumulates instead as lactate. One problem with this theory however, is that despite the increase in plasma free fatty acids observed by the authors, there was no apparent increase in lipid oxidation. The latter would be expected to be required to inhibit PDH. In any case, by whatever mechanism, GH administration clearly adversely affected cycling performance in this experiment.

    Although the research described above looked at the acute effects of GH administration on athletic performance, there are chronic effects as well that could be detrimental to the athlete. Insulin resistance is a common side effect of GH use and would be expected to reduce glucose availability to muscle. GH administration also results in the impairment of muscle and liver glycogen storage. These latter effects, limited liver and muscle glycogen storage, could have a serious impact on recovery from strenuous exercise, as well as negatively impact performance itself as a result of decreased glycogen availability. The edema associated with GH administration could also impair athletic performance, as might the arthralgia experienced by many GH users. Rennie even cites the possibility that the fatty acidemia resulting from GH-induced lipolysis could promote cardiac arrhythmia during intense exercise. Although remarks such as this are reminiscent of some of the hyperbole from the medical community regarding anabolic steroids, there is probably some degree of legitimacy to the concerns of Rennie and others who have stressed the potential seriousness of GH related side effects. Athletes should at least be aware that concern exists over such things as potentially fatal as arrhythmia.

    In addition to the potentially detrimental derangements in glucose metabolism mentioned above, GH administration in humans has been shown to induce a shift in muscle fiber type from type 2a to 2x (9, 10). The latter has been characterized as the “default? fiber type since the proportion of 2x fibers to type1 and type 2a is relatively high in “couch potatoes? compared to strength and power athletes. Resistance training induces a shift in the opposite direction from type 2x to 2a. During detraining, the muscle fiber type shifts back to 2x. The training induced shift is interpreted as an adaptive mechanism to the increased demands placed upon the muscle. If GH administration induces a shift in muscle fiber type away from the trained state, this could have negative implications for strength and power athletes.

    Why, in light of all this negative evidence for any strength or muscle mass increase resulting from exogenous GH, is the bodybuilding literature replete with anecdotal reports of impressive gains in muscle mass and strength? And what motivates athletes to use GH in light of the negative research and side effects? One obvious possibility is that the research results are wrong or incomplete. But assuming they are not for the sake of furthering the discussion, another conceivable explanation for the reported gains in muscle mass are the lipolytic effects of GH discussed above. Bodybuilders could easily be mistaking enhanced definition for an increase in muscle. GH associated water retention could also add to the feeling that mass has increased. Certain anabolic steroids such as Dianabol and Deca Durabolin are notorious for causing water retention. These same drugs also have a reputation for increasing the resistance exercise induced muscle “pump?, contributing to a feeling of increased strength. The water retention from exogenous GH could have the same effect. Additionally, athletes and even researchers have noted that in elite athletes, studies would probably be unable to detect with statistical significance a 1 or 2 percent increase in performance that could result from GH use, and would make all the difference in the world to an elite athlete. Arguing against this is the observation that performances in a number of Olympic events such as shotput, discus, and javelin, particularly among women, have deteriorated since routine testing for anabolic steroids was implemented. It is very likely that these athletes who formerly were heavy users of anabolic steroids are now using rhGH, but it does not seem to be helping their performance. And perhaps the most obvious reason that many athletes and bodybuilders use GH is that the competition is using it.

    In summary, despite numerous anecdotal reports to the contrary, to quote from (7),

    The results of studies of muscle protein synthesis, body composition, and strength in healthy young to middle aged humans tell a different tale: so far no robust, credible study has been able to show clear effects of either medium to long term rhGH administration, alone or in combination with a variety of training protocols or anabolic steroids, on muscle protein synthesis, mass or strength.

    These results, coupled with the possibility that GH use could significantly compromise training and performance, as described in (8), make a fairly strong argument against the use of GH in sport.


    (1) Yarasheski KE, Zachweija JJ, Angelopoulos TJ, Bier DM Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J Appl Physiol. 1993 Jun;74(6):3073-6.

    (2) Fryburg DA, Gelfand RA, Barrett EJ. Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans. Am J Physiol. 1991 Mar;260(3 Pt 1):E499-504

    (3) Fryburg DA, Louard RJ, Gerow KE, Gelfand RA, Barrett EJ. Growth hormone stimulates skeletal muscle protein synthesis and antagonizes insulin's antiproteolytic action in humans. Diabetes. 1992 Apr;41(4):424-9

    (4) Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO, Bier DM. Effect of growth hormone and resistance exercise on muscle growth in young men. Am J Physiol. 1992 Mar;262(3 Pt 1):E261-7

    (5) Deyssig R, Frisch H, Blum WF, Waldhor T. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Acta Endocrinol (Copenh). 1993 Apr;128(4):313-8.

    (6) Crist DM, Peake GT, Egan PA, Waters DL. Body composition response to exogenous GH during training in highly conditioned adults. J Appl Physiol. 1988 Aug;65(2):579-84.

    (7) Rennie MJ.Claims for the anabolic effects of growth hormone: a case of the emperor's new clothes? Br J Sports Med. 2003 Apr;37(2):100-5.

    (8) Lange KH, Larsson B, Flyvbjerg A, Dall R, Bennekou M, Rasmussen MH, Orskov H, Kjaer M. Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men. J Clin Endocrinol Metab. 2002 Nov;87(11):4966-75.

    (9) Hennessey JV, Chromiak JA, DellaVentura S, Reinert SE, Puhl J, Kiel DP, Rosen CJ, Vandenburgh H, MacLean DB. Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people. J Am Geriatr Soc. 2001 Jul;49(7):852-8.

    (10) Lange KH, Andersen JL, Beyer N, Isaksson F, Larsson B, Rasmussen MH, Juul A, Bulow J, Kjaer M. GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab. 2002 Feb;87(2):513-23
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  11. Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters.

    Yarasheski KE, Zachweija JJ, Angelopoulos TJ, Bier DM.

    Metabolism Division, Washington University School of Medicine, St. Louis, Missouri 63110.

    The purpose of this study was to determine whether recombinant human growth hormone (GH) administration enhances muscle protein anabolism in experienced weight lifters. The fractional rate of skeletal muscle protein synthesis and the whole body rate of protein breakdown were determined during a constant intravenous infusion of [13C]leucine in 7 young (23 +/- 2 yr; 86.2 +/- 4.6 kg) healthy experienced male weight lifters before and at the end of 14 days of subcutaneous GH administration (40 microgram.kg-1 x day-1). GH administration increased fasting serum insulin-like growth factor-I (from 224 +/- 20 to 589 +/- 80 ng/ml, P = 0.002) but did not increase the fractional rate of muscle protein synthesis (from 0.034 +/- 0.004 to 0.034 +/- 0.002%/h) or reduce the rate of whole body protein breakdown (from 103 +/- 4 to 108 +/- 5 mumol.kg-1 x h-1). These findings suggest that short-term GH treatment does not increase the rate of muscle protein synthesis or reduce the rate of whole body protein breakdown, metabolic alterations that would promote muscle protein anabolism in experienced weight lifters attempting to further increase muscle mass.
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  12. Effect of growth hormone and resistance exercise on muscle growth in young men.

    Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO, Bier DM.

    Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

    The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function.
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  13. In regards to hormones and exercise selection. Can you not get the same response from doing leg press?

  14. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes.

    Deyssig R, Frisch H, Blum WF, Waldhor T.

    Department of Paediatrics, University of Vienna, Austria.

    The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4 +/- 0.5 years; ideal body weight 122 +/- 3.1%, body fat 10.1 +/- 1.0%; mean +/- SEM) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)-1 day-1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding proteins, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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  15. Claims for the anabolic effects of growth hormone: a case of the Emperor’s new clothes?
    M J Rennie

    Correspondence to:
    Professor Rennie, Division of Molecular Physiology, Faculty of Life Sciences, Old Medical School, University of Dundee, Dundee DD1 4HN, Scotland, UK;
    [email protected]

    Accepted 2 December 2002

    This review examines the evidence that growth hormone has metabolic effects in adult human beings. The conclusion is that growth hormone does indeed have powerful effects on fat and carbohydrate metabolism, and in particular promotes the metabolic use of adipose tissue triacylglycerol. However, there is no proof that net protein retention is promoted in adults, except possibly of connective tissue. The overexaggeration of the effects of growth hormone in muscle building is effectively promoting its abuse and thereby encouraging athletes and elderly men to expose themselves to increased risk of disease for little benefit.


    Keywords: muscle; anabolism; growth hormone; abuse

    Abbreviations: GH, growth hormone; rhGH, recombinant human growth hormone; IGF-I, insulin-like growth factor I

    A search of the internet for the words "growth hormone" will bring up a large number of hits, and most of these have very little to do with the actual physiology or pharmacology of growth hormone (GH) or the recombinant form manufactured as a drug (rhGH). Instead, the search engine will identify a large number of URLs leading to web pages, most of which promote GH as either a rejuvenating agent for middle aged and elderly men and women or as a muscle building agent for body builders and athletes. The link between the two is the widespread supposition that administration of exogenous GH will build muscle mass in adult humans. Some web sites advocate the use of GH itself. True pharmaceutical grade human GH (hGH) preparations are available for self administration after registration in the United States as a patient in one of many online clinics, or by making a trip into Mexico from the United States. Black market injectable rhGH—some of cadaveric origin—is also widely available in the body building and professional athletic communities. Nasal sprays (of doubtful efficacy) are available from many online suppliers, as are nutritional supplements claimed (on no visible evidence) to cause anabolism indirectly, as a result of increased GH secretion. Examples of the claims made are shown below: "Product X is a high concentration real Pharmaceutical Grade Recombinant Human Growth Hormone solution (2040 ng/ml.) The product comes with a patented delivery system, that really works allowing complete HGH absorption and in raising IGF-I levels and restoring total youthful homeostasis. Recent double blind clinical studies have shown a 30% increase in IGF-I levels after just one month of use with Product X and over 110% increase after just six months of use". For GH releasers, typical claims include: "Product Y contains the human unique growth hormone releasing formula used in the famous Rome experiments. For many users this synergistic combination of Arginine, Pyroglutamate and Lysine is the most potent HGH releaser, dramatically raising IGF-I levels for a solid eight hours after use! The low price and great results has made Product Y the HGH product of choice for many anti-aging programs." Or: "Our proprietary formula—Product Z—will naturally "kick start" your pituitary gland providing everything it needs to restore HGH pulses to youthful levels! When this happens your body then has the IGF-I it needs for tissue, bone and muscle repair—this is why some call it "turning back the clock." And: "Product Z is the best product to achieve very rapid increases in human growth hormone levels. It is also a favorite among body builders." None of the claims made can be substantiated by publications in the peer reviewed literature, usually because the companies do not cite the papers, and, when they do, the papers are of poor quality. There are a large number of problems here, but the one of most concern is the extent to which the scientific and medical community interested in sports is effectively promoting the use of a substance with potentially severe side effects by uncritically accepting the proposition that GH is anabolic in healthy adults. This proposition is actually reinforced by efforts to justify the development of methods to detect exogenous GH in human body fluids—for example, the IOC/EC sponsored GH2000 study—and by, for example, describing GH as "the most anabolic substance known", as was claimed in the publicity for the recent UK Royal Society of Chemistry sponsored conference on drugs in sport (http://www.rsc.org/pdf/confs/symp230502.pdf).

    In fact, as is argued below, the evidence that GH is anabolic in healthy adults is very poor. Furthermore, there is good evidence that chronic high serum concentrations of GH decrease performance and acutely may even cause metabolic changes in the short term that are likely to diminish the capacity for strenuous physical activity. Perhaps most worryingly, high dose chronic hGH administration in normal adults may lead to metabolic alterations that are associated with a number of deleterious side effects such as cardiac instability, hypertension, and the development of insulin resistance and possibly type 2 diabetes, many of which are suffered by patients who produce excess growth hormone as a result of pituitary tumours—that is, acromegaly—and by patients receiving rhGH in an attempt to combat wasting caused by HIV/AIDS.

    GH is secreted in a pulsatile fashion from the anterior hypophysis, beneath the hypothalamus in the brain. As a result of alternative splicing and proteolytic processing, a number of different immunoreactive species, are secreted into the blood.1 The relative efficacy of the binding of each molecular species to the GH receptors and the extent of the subsequent physiological and pharmacological effects are known for only the major forms of the hormone and are almost certainly not uniform.1,2 During human development, GH secretion is maximal during periods of growth, most obviously adolescence; thereafter both the periodicity and amplitude of GH secretion falls at a relatively low rate—for example, the total amount of GH secreted by a 60 year old man each day may be about half that secreted by a 20 year old.3 GH secretion usually occurs nocturnally,4 but may be stimulated during the day by high protein foods, especially those containing arginine,5 and by exercise of both the aerobic and resistance types.6–9 Apart from sleep, exercise is the most potent physiological stimulus of GH secretion, and, although it is well characterised, the underlying mechanisms and its telenomic role are still largely unknown. The extent of the exercise induced stimulation of GH secretion appears to be proportional to the intensity of exercise10 because of alterations in amplitude of secretory pulses. Women appear to secrete more GH than men at the same intensity of exercise.11 Preceding exercise sensitises GH secretion, so that repeated exercise results in a greater response per bout.12 The total amount of GH secretion tends to be greater with moderate dynamic exercise than with resistance exercise,8 possibly simply because it continues longer. These two characteristics are inconsistent with GH being responsible for an adaptive response in muscle bulk because women have less muscle than men and aerobic exercise is associated with alterations in muscle composition not bulk. Obesity and aging also diminishes normal GH secretion and the response to stimuli such as arginine and clonidine.3,13,14 The ability to increase GH with exercise is diminished with obesity and aging,9,15 but is certainly not abolished in either case.

    This area has been recently reviewed.16 Most of the anabolic effects of GH are not direct metabolic effects on target tissues such as muscle, but are in fact the result of increased production of insulin-like growth factor I (IGF-I) from the liver (as a consequence of which the serum concentration of IGF-I is increased) as well as the production of IGF-I in tissues that are responsive to GH such as bone and muscle.17 In growing animals, in children, and in adults with GH deficiency, GH is very anabolic, causing increases in bone and muscle mass.18–20

    GH probably stimulates the hypertrophy of muscle in young animals and children, as a result of IGF-I stimulation of (a) amino acid transport,21,22 (b) the translational stage of protein synthesis,22 and (c) gene transcription,23 all actions appropriate to tissue building. It also stimulates the growth of the long bones as a result of increasing osteoblast activity in the post-epiphyseal region of bones that have not yet fused.18

    In addition to its effects mediated by IGF-I, GH greatly stimulates lipolysis in adipose tissue,24 both central and peripheral, by an IGF-I independent mechanism. The effects of free fatty acids in inhibiting uptake of glucose into heart, adipose tissue, and muscle are at least partly responsible for the hyperglycaemia and insulin resistance associated with rhGH administration.25,26 GH inhibits glycogen storage in liver and muscle27 by a mechanism that lies beyond the insulin receptor.26 Somewhat paradoxically, IGF-I alone has an acute insulin-like hypoglycaemic effect.28 However, this effect appears to be usually overridden during chronic rhGH treatment.29

    Furthermore, GH causes increased water absorption by the gut and increased sodium retention probably by activation of the renin-angiotensin system.30–32 This can lead to extracellular fluid accumulation and, in some cases, also to carpal tunnel syndrome as well as elevated blood pressure at high doses.

    There is no doubt whatsoever that exogenous GH (nowadays always rhGH) can have a considerable beneficial effect in restoring growth in GH deficient children and short, apparently normal children, children with kidney disease, and babies born when short for gestational age.33–37 In true GH deficiency and renal disease, treatment results in a greater final height, but in idiopathic short stature or in children who are short for gestational age, the benefit seems to be confined to accelerating growth, not increasing the final height achieved. The accelerated growth is associated with rapid increases in energy expenditure and protein turnover, as expected.19,38,39

    The administration of rhGH to patients suffering from sepsis and trauma, although hailed as a way of controlling the pronounced wasting observed in such patients, is now rare, after a first flush of enthusiasm in the mid to late 1990s.40,41 This is because in a large multicentre trial of rhGH in patients in intensive care units, there was a substantial excess mortality associated with the treatment group.39,42 The reason has never been adequately identified, but one strong possibility is cardiac instability precipitated by elevated plasma free fatty acid concentrations resulting from the lipolytic effect of GH. The use of rhGH in such circumstances is now regarded as risky.

    In elderly subjects who are GH deficient, short term administration of rhGH or IGF-I increases the rate of muscle protein synthesis.43 Chronic administration of rhGH was reported to reduce body fat and also increase lean body mass—that is, irrespective of fat loss—in GH deficient men.44–47 One of the odd features of this work is that no changes in quadriceps muscle fibre area or fibre type or distribution of fibre types were associated with the reported increase in lean body mass despite claimed increases in thigh muscle cross sectional area measured by computed x ray tomography.

    The use of rhGH in patients with wasting caused by HIV/AIDS has grown dramatically in the past 10 years,29 but evidence of efficacy in regrowing or even maintaining muscle is as yet lacking.

    It has been speculated that the increased GH secretion in humans would serve as an anabolic signal to increase muscle mass and upregulate the adaptations that occur with exercise training. This hypothesis is supported by the results of many animal studies, in which GH administration causes substantial increases in both muscle mass and strength. In these studies, however, the animals involved were probably still growing and sensitive to both GH and IGF-I.

    Acute administration of rhGH or IGF-I in normal healthy humans in the postabsorptive state is reported to acutely increase forearm net balance of amino acids.48,49 The effects are claimed to occur through the stimulation of protein synthesis rather than a fall in protein breakdown. No similar studies were carried out in the fed state, and the lack of reports of any longer term effects (see below) seems to suggest that this anabolic stimulus is short lived. The results of studies of muscle protein synthesis, body composition, and strength in healthy young to middle aged humans tell a different tale: so far, no robust, credible study has been able to show clear effects of either medium to long term rhGH administration, alone or in combination with a variety of training protocols or anabolic steroids, on muscle protein synthesis, mass, or strength.

    There are a number of ways in which an effect of GH on muscle growth may be detected. These include measurement of lean body mass by densitometry or by dual x ray absorptiometry. As the rate of muscle protein turnover is relatively slow, it is relatively difficult to detect increases in muscle mass per se over periods shorter than three months using such static techniques, even if the rate of muscle growth is doubled. Measuring the rate of protein synthesis as the rate of incorporation of amino acids labelled with stable isotopes into muscle rather than simply the changes in muscle mass between two points is a much more sensitive method for determining the response of muscle. When this has been done in young healthy adults, no effect on muscle protein synthesis (or indeed on muscle mass measured by other means) has been detected.50 Furthermore, no effect has been detected in body builders and weightlifters.51,52 Thus, at the very least, it appears that the evidence for a sustained anabolic effect of rhGH on muscle mass in normal healthy young men, trained or untrained, is extremely slim.

    It has been suggested that, because GH secretion and thus IGF-I availability falls with age, rhGH administration should be beneficial in elderly men in decreasing adiposity and increasing lean body (principally muscle) mass. Indeed Rudman and coworkers53,54 reported evidence that this was so; however, reproduction of these results by other workers has proven difficult. For example, in healthy middle aged to elderly men, administration of rhGH appears to cause no increase in muscle mass or strength55,56 unless it is associated with resistance training. Indeed it appeared that the benefits of exercise in terms of increased glucose tolerance were negated by rhGH in the elderly subjects. Supporting evidence of a lack of effects on elderly, but not particularly GH deficient, men was provided by Taffe and coworkers,57,58 who were unable to see any increases in strength or muscle mass or fibre characteristics after rhGH supplementation during a resistance exercise training programme. Recently, a wide ranging study of the effects of rhGH alone or combined with resistance training on muscle strength, power, muscle cross sectional area, and fibre size and mass in elderly men was unable to show any positive effects except in increasing the expression of myosin heavy chain type 2x.59,60

    Despite the excitement of the early days, there also appear to be no discernible effects on skeletal muscle mass or function in healthy elderly subjects, even with testosterone co-administration. The most recent paper available on this topic described the effects of testosterone, rhGH, or the two together in elderly men.61 The authors concluded that, after rhGH or rhGH together with testosterone, apart from the apparent increases in lean body mass of a type criticised above, there were only marginal increases in muscle strength and small increases in oxygen consumption.

    It is possible that some workers have confused decreases in fat mass with increases in lean body mass, or have assumed muscle and lean body mass are equivalent. It may also be that rhGH administration causes increases in body water and connective tissue, which are registered as alterations in lean body mass. The overwhelming majority of reports suggesting that rhGH has an anabolic effect in adults come from studies of GH deficient patients.

    A number of previous reviewers have made some similar points to those raised here.62–64

    Are scientists and doctors using too little hGH to see the effects that athletes achieve by using large doses? This is of course a possibility; by analogy, it was many years before scientists and doctors accepted that the anabolic effects of testosterone and its analogues were real—see, for example, the careful work of Forbes.65 Nevertheless, in my view the possibility is slight. Anecdotal evidence suggests that many hGH abusers, especially those taking the hormone without medical supervision, do inject supratherapeutic doses. However, in most of the studies in the literature, effects of hGH were also studied at greater than the therapeutic dose, and although these may well have been below the dosages used by abusers, they still resulted in serum concentrations of GH and IGF-I that were 3–6 times normal55,56 and that resulted in pronounced biological effects, such as increased lipolysis, altered carbohydrate metabolism, activation of the renin-angiotensin system, and water retention. It is difficult to believe that, even for effects that are not IGF-I mediated (such as the lipolytic effects), muscle tissue is IGF-I resistant to this extent.

    Furthermore, when extremely large therapeutic doses of rhGH are used—for example, in the attempted treatment of wasting in HIV/AIDS—it appears to be much easier to induce diabetic symptoms than retention or recovery of lean body mass.29,66 This, of course, may be a feature of a GH resistant syndrome, but it is odd that there is such a separation between biological effects of the same substance.

    Nevertheless, it is relatively easy to see effects of other biological agents that do have effects on muscle protein turnover at blood concentrations that are observed biologically, and without using massive pharmacological doses. For example, insulin has substantial effects on protein synthesis and breakdown in muscle67–69 at concentrations seen after meals. As a further illustration, a modest rise in blood amino acids such as is seen after feeding causes a near doubling of muscle protein synthesis.67,69 Why should a dose of rhGH, which can more than double serum IGF-I and cause considerable effects on body water, fat free mass, and nitrogen balance,50,51,56 be insufficient to have an effect through IGF-I on muscle protein metabolism? It would, arguably, be a very unbiological pattern of behaviour.

    Does the increased nitrogen retention often reported to be observed with rhGH administration50 not argue for an effect on muscle, the largest component of the lean body mass? Not necessarily. Apart from anabolic effects in viscera and skin,70,71 rhGH has been reported to have anabolic effects on collagen metabolism,20,72 and even when bone is excluded from measurements of lean body mass using dual x ray absorptiometry, the epimysial, endomysial, and perimysial collagenous components of skeletal muscle and connective tissue elements of skin may all show up as new lean body mass. A modest increase in skin, visceral protein and tissue (including muscle) collagen would translate into a sizeable positive nitrogen balance.

    Such an effect on connective tissue in muscle would make the muscle no more capable of force generation but may promote resistance to injury or faster repair, which would be an advantage to an athlete. This may explain the anecdotally reported predilection of baseball players for abuse of testosterone and rhGH together. Unfortunately this possible synergism has never been studied under control circumstances in young men. Certainly co-administration of testosterone and rhGH has only a minor effect on strength in elderly men.61

    If there were a threshold in the supraphysiological range for an anabolic effect of rhGH on muscle, it would be expected that patients with acromegaly would show true muscle hypertrophy. In fact, the lack of appreciably greater muscle mass per height as well as associated pathological changes (see later) argues against this idea. This is reinforced by the finding that transgenic mice overexpressing GH show no relative increase in muscle mass as a fraction of total body weight, and what muscle they have develops less force than expected on a weight basis.73

    Thus, the balance of evidence seems to be heavily against an anabolic effect of rhGH on human muscle. It may seem that the only way to settle the question in the minds of champions of the use of rhGH is to carry out a dose-response study with large amounts of the hormone. This is easier said than done: we need to discover what amounts abusing athletes inject (it will always be easy to say that what was used was insufficient) to target an appropriate dose range while staying within normal ethical limits given the cardiovascular and metabolic hazards involved.

    The acute administration of rhGH may have appreciably detrimental effects on performance. In fact, there is good evidence that acute administration of rhGH actually results in a decrease in exercise performance according to recent results obtained by Dr Kai Lange of the Danish Institute of Sports Medicine (personal communication). In these studies, healthy endurance trained athletes were unable to complete accustomed cycling tasks after administration of exogenous hGH. There is good evidence that hGH administration exacerbates the pronounced increase in lipolysis that occurs during exercise and, in addition, increases the production of lactate and protons by working muscles. The inevitable metabolic acidaemia and consequent reduction in the rate of glycogenolysis in muscle and liver could explain the acutely decreased performance. Furthermore, because of the effect of rhGH in decreasing glycogen storage in muscle and liver, it will make recovery from exercise more difficult. However, a bigger danger is probably the unphysiologically high fatty acidaemia, which could promote cardiac arrhythmia.

    Chronic rhGH abuse is more dangerous. As most athletes are likely to be using suprapharmacological amounts, the correct model in which to look for such deleterious effects is not the adult GH deficient patient given replacement therapy, but patients suffering from acromegaly—that is, with an excess of GH secretion, often 100 times normal. These patients have poor exercise tolerance, which improves after treatment to decrease GH secretion.74 However, they show little evidence of true muscle hypertrophy in terms of creatinine to height ratios or muscle cross sectional areas, but often exhibit a number of myopathic features such as increased plasma creatine kinase, raised type 2 to type 1 muscle fibre areas, type 2 fibre atrophy, and myofilament loss as well as myopathic electrophysiological changes.75 Furthermore, patients with acromegaly have considerably increased rates of cardiovascular disease, diabetes, abnormal lipid metabolism, osteoarthritis, and breast and colorectal cancer.63 The concentrations of free fatty acids stimulated by exercise in these patients76 is in the range suggested by Opie77 to be a possible cause of sudden death from arrhythmia.

    Another frightening problem is that, as supplies of bioengineered rhGH become more controlled, athletes are tempted to use the hormone obtained illegally from cadavers,78 risking the inevitably fatal Creutzfeldt-Jakob disease.

    If rhGH administration under controlled conditions has no stimulatory effect on muscle protein synthesis in adult humans, as the weight of evidence suggests, and confers no short term advantages as an acute ergogenic aid, why do athletes abuse it? There are probably three answers. Firstly, the effects on salt and water balance occur quickly, and athletes abusing rhGH are able to tell—for example, by proprioceptive effects in joints and muscles—that "something" has happened as a result of using it. This has a positive reinforcing effect, and so they continue to take the drug. Secondly, there is no doubt that rhGH has what meat production experts call a "repartitioning" effect, in decreasing subcutaneous fat—the lipolytic effect being sufficiently powerful for athletes to perceive the resulting improvement in muscle definition (not actually muscle growth) relatively quickly. This is, no doubt, part of the reason rhGH is popular with body builders, but it is irrelevant to the argument about anabolic effects on muscle. In any case most elite athletes have low body fat, so it is doubtful whether any small increase in power to weight ratio as the result of loss of more fat could be significant in terms of increased performance.

    Take home message
    The balance of evidence suggests that, in healthy adults, growth hormone does not build muscle and provides no athletic advantage. Growth hormone abuse, however, does cause disease. This message needs to be taken on board by coaches, team doctors, and potential abusers.

    Thirdly, there is the question of the disinformation on rhGH that envelopes young athletes. Part of this problem may, paradoxically, derive from the anti-doping authorities themselves. By ignoring the evidence that rhGH does not work in normal healthy subjects, the athletic establishment could be accused of effectively promoting its use. It is laudable to fund the development of a test that will be accurate, precise, and selective, so that those tempted to abuse rhGH will think twice. Sadly this has not happened, and instead large amounts of money have been spent in developing tests for GH that are probably insufficiently selective and sensitive and too cumbersome for practical use.79,80 The failure was probably predictable, given the flawed strategy used in looking for biological indices (IGF-I and bone markers), which are too variable to satisfy the purpose. Investment in a proper education programme, which highlighted the available evidence, would have brought greater benefits.

    We must tell athletes the truth: growth hormone does not "work" or at least not as they think it does and that it is associated with all kinds of immediate and long term hazards—everything from decreased performance to cancer. The benefits in terms of decreased subcutaneous fat are minor by comparison. The International Olympic Committee and the World Anti-Doping Agency and other national and international sporting bodies should sponsor programmes of research to settle outstanding important questions—for example, synergy of GH and anabolic steroids, dose-response relations—once and for all. All expenditure to improve tests for GH should be subordinate to the research and education programme, but in the meantime none of us, scientists, doctors, coaches, or sports bodies, should connive to suggest that this dangerous doping practice works. It almost certainly does not.
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  16. GH Administration Changes Myosin Heavy Chain Isoforms in Skeletal Muscle But Does Not Augment Muscle Strength or Hypertrophy, Either Alone or Combined with Resistance Exercise Training in Healthy Elderly Men
    Kai Henrik Wiborg Lange, Jesper Løvind Andersen, Nina Beyer, Fredrik Isaksson, Benny Larsson, Michael Højby Rasmussen, Anders Juul, Jens Bülow and Michael Kjær
    Sports Medicine Research Unit (K.H.W.L., N.B., F.I., M.K.), Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark; Copenhagen Muscle Research Centre (K.H.W.L., J.L.A.), Department of Molecular Muscle Biology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark; Team Danmark Test Center (B.L.), Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark; Clinical Drug Development (M.H.R.), Novo Nordisk, DK-2880 Bagsvaerd, Denmark; Department of Growth and Reproduction (A.J.), Rigshospitalet, DK-2100 Copenhagen Ø, Denmark; and Department of Clinical Physiology (J.B.), Bispebjerg Hospital, DK-2400, Copenhagen NV, Denmark

    Address all correspondence and requests for reprints to: Kai H. W. Lange, M.D., Sports Medicine Research Unit, Building 8, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. E-mail: [email protected].


    GH administration, either alone or combined with resistance exercise training (RT), has attracted interest as a means of increasing muscle mass and strength in the elderly. In the present study, 31 healthy, elderly men [age, 74 ± 1 yr (mean ± SEM)] were assigned to either RT [3 sessions/wk, 3–5 sets of 8–12 repetition maximum (RM)/session] + placebo (n = 8), RT + GH (n = 8), GH (n = 8), or placebo (n = 7) in a randomized, placebo-controlled, double-blinded (RT + placebo and RT + GH) or single-blinded (GH or placebo) design. Measurements of: 1) isokinetic quadriceps muscle strength; 2) quadriceps muscle power; 3) quadriceps muscle fiber type, size, and myosin heavy chain (MHC) composition; 4) quadriceps cross-sectional area (CSA) [nuclear magnetic resonance imaging (NMRI)]; 5) body composition (dual-energy x-ray absorptiometry scanning); and 6) GH-related serum markers were performed at baseline and after 12 wk. The final GH dose was 1.77 ± 0.18 IU·d-1 (7.2 ± 0.8 µg·kg-1·d-1). GH alone had no effect on isokinetic quadriceps muscle strength, power, CSA, or fiber size. However, a substantial increase in MHC 2X isoform was observed with GH administration alone, and this may be regarded as a change into a more youthful MHC composition, possibly induced by the rejuvenating of systemic IGF-I levels. RT + placebo caused substantial increases in quadriceps isokinetic strength, power, and CSA; but these RT induced improvements were not further augmented by additional GH administration. In the RT + GH group, there was a significant decrease in MHC 1 and 2X isoforms, whereas MHC 2A increased. RT, therefore, seems to overrule the changes in MHC composition induced by GH administration alone. Changes in body composition confirmed previous reports of decreased fat mass, increased fat-free mass, and unchanged bone mineral content with GH administration. A high incidence of side effects was reported. Our results do not support a role for GH as a means of increasing muscle strength or mass, either alone or combined with RT, in healthy elderly men; although GH administration alone may induce changes in MHC composition.

    GH IS AN anabolic hormone capable of increasing muscle mass ( 1). This has been demonstrated clearly in animals, using different models combining GH administration, hypophysectomi, hindlimb suspension, and casting (immobilization) ( 2, 3, 4, 5, 6, 7). In humans, GH administration is known to increase both whole-body and muscle protein synthesis ( 8, 9, 10) and almost unequivocally to increase lean body mass (LBM) and decrease FM ( 11, 12, 13, 14, 15, 16, 17). GH administration has therefore attracted great interest, in the past decade, as a means of increasing LBM and muscle strength, either alone or in combination with different training regimens ( 17, 18, 19, 20, 21). Investigations have predominantly focused on the elderly population, because it is known that the elderly have a decreased function of the GH-axis, and this has been proposed to play a causative role in the decreased muscle mass and strength also observed in the elderly ( 22). Furthermore, if such a causal relationship between GH administration and muscle function exists, the elderly would obviously be the target population that would benefit the most from GH administration.

    In patients with GH deficiency, some reports have demonstrated small increases in muscle strength ( 23, 24) and endurance ( 16, 25) with GH therapy. Nevertheless, results have not been encouraging in healthy elderly subjects. Despite undisputed increases in LBM, GH administration alone does not seem to increase aerobic performance [maximal oxygen uptake (VO2max)] or muscle strength in elderly men ( 26) or women ( 27). Furthermore, GH administration, combined with different resistance exercise training (RT) regimens in elderly men, did not augment the strength improvements induced by training alone in two of the three reports published so far ( 17, 19). In one report, however, Welle et al. ( 20) found a significant effect of GH administration on muscle strength when combined with RT in elderly men. Although differences in study design exist, these conflicting results are not immediately intelligible.

    Investigations in healthy elderly human subjects, with respect to the effects of GH administration on muscle function, are very limited in number. To our knowledge, the effects of GH administration alone has only been reported in the study by Papadakis et al. ( 26) (n = 26 receiving GH), and only three reports have studied the effects of GH administration combined with RT (n = 10 + 8 + 6 = 24 receiving GH), the latter three giving conflicting results ( 17, 19, 20).

    With this background, we conducted a randomized, placebo-controlled, partially double-blinded RT study in elderly men. Furthermore, because no information is available on changes in myosin heavy chain (MHC) composition in this context, we also focused on this issue, because skeletal muscle MHC composition has been shown to correlate with functional muscle characteristics on both single-fiber ( 28) and whole-muscle levels ( 29). Thirty healthy men (>70 yr old) completed a 12-wk supervised RT program, having been assigned to either RT + placebo, RT + GH, GH alone, or placebo alone. We hypothesized that GH administration alone would increase muscle mass and strength and that GH administration combined with RT would increase muscle mass and strength more than RT alone. Furthermore, we hypothesized that GH alone or combined with RT would induce changes in skeletal muscle MHC composition.

    Materials and Methods


    Thirty-one healthy, elderly male subjects were included in the study; age, 74 ± 1 yr (70–82) [mean ± SEM (range)]; height, 174 ± 1 cm (163–186); body weight, 80.8 ± 1.8 kg (63.1–100.3); body mass index, 26.7 ± 0.5 kg·m-2 (20.9–32.8); body fat, 22.9 ± 1.2 kg (10.9–38.9), 28.0 ± 1.0% (14.9–40.0). Before inclusion, each subject underwent a comprehensive medical evaluation, including medical history, physical examination, routine blood tests, and an exercise electrocardiogram. Exclusion criteria were metabolic, cardiac, and malignant disease; anemia; hormonal replacement therapy; and medication with - or ß-blockers.

    Ethical approval

    Informed consent was obtained according to the Helsinki 2 declaration, and the study protocol was approved by the Ethics Committee for Medical Research in Copenhagen (KF 02-130/97) and by the Danish National Board of Health (journal no. 5312-181-1997).

    Experimental protocol

    After inclusion, the subjects were randomized, in blocks of four, to either RT or no training and to receive either GH or placebo. Because not all measurements were performed in the group receiving only placebo, the principal investigator was not blinded with respect to the two groups assigned to no training. In this way, GH administration was double-blinded in the two training groups and single-blinded in the two groups assigned to no training. The subjects in the training groups subsequently underwent a 12-wk supervised strength training program. Measurements were made at baseline and after 5 and 12 wk of training and/or GH/placebo administration. The blinding was maintained until data acquisition was completed for the whole study.

    Administration of recombinant human GH

    Recombinant human GH or placebo (GH, Norditropin PenSet 24; placebo, Norditropin PenSet 24 Placebo; both from Novo Nordisk, Denmark) was administered sc in the thigh, one time per day. Both drug and injection devices were similar for placebo and GH. After thorough instruction, the subjects were able to perform the injections themselves at home, in the evening, before bedtime. Syringes and injection technique were reviewed weekly by a trained technician to ensure compliance. At the commencement of the study, the dose was increased, over 3 wk, to avoid side effects. During the first week, the dose was 0.5 IU·m-2; during the second week, 1.0 IU·m-2; and for the remaining of the period, 1.5 IU·m-2 (12 µg·kg-1·d-1). The subjects were weighed, checked for edema, and questioned about side effects every week by the same physician. If side effects appeared, the dose was reduced by 50%, until the side effects had disappeared or were tolerable to both the subject and the investigators.

    Determination of peak oxygen uptake (VO2 peak)

    VO2 peak was determined, at baseline, on an electromagnetically braked bicycle ergometer (Technogym, Bikerace, Gambettola, Italy). A protocol starting at 40 W and increasing with 20 W every 2 min until exhaustion was used. Respiratory variables were measured using an AMIS 2001 automated metabolic cart (INNOVISION, Odense, Denmark) and were averaged for each 15-sec period. The mean of the two highest 15-sec values was recorded as VO2 peak.

    Dual-energy x-ray absorptiometry (DEXA)

    Body composition was determined by DEXA scanning at baseline and after 12 wk. The subjects were scanned, in the morning, after an overnight fast and after having emptied the urine bladder. A DPX-IQ scanner (Lunar Corp., Madison, WI; software version 4.6 C) was used, and the scans were performed at baseline and after 12 wk of training/GH administration. A medium scanning procedure (25 min) was chosen, and the same two trained technicians performed all scans. The same investigator analyzed all scans, using the extended research analysis software provided by Lunar Corp. In the analysis, total body scan was divided into three regions: arms, legs, and trunk. Total and regional scans were further divided into three compartments: fat free mass (FFM), FM, and bone mineral content (BMC).

    Muscle biopsies

    Muscle biopsies were obtained from the right vastus lateralis muscle, at midthigh level, at baseline and after 12 wk. Sampling was performed in the morning, after an overnight fast; and, in the two training groups, the 12-wk biopsies were obtained 24 h after completion of the last training session. Sampling at 12 wk was performed, 1 cm proximal to baseline sampling. The overlying skin was anesthetized with 1% lidocaine, and sampling was done through an incision using a 5-mm Bergström needle ( 30). A suction device, in conjunction with the biopsy needle, was used to create a negative pressure while sampling, which allowed for a larger sample specimen. Muscle samples were immediately mounted in tissue-tek, frozen in isopentane cooled with liquid N2, and transferred to vials for storage at -80 C until analysis. Biopsies were not obtained from the group receiving only placebo.

    Leg extensor power

    Measurement of leg extensor power was performed at baseline and after 12 wk in a Nottingham Power Rig, as reported previously ( 31). The subject was in a seated position, and single explosive efforts of the leg extensors accelerated a flywheel from rest. The final speed of the flywheel was used to calculate average power. Measurements were repeated, with a minimum of 10 trials or until no further improvements were observed. Each leg was tested separately, and verbal encouragement and visual feed-back were given. The average of the 3 best trials of the right leg was used as a measure of the maximal leg extensor power.

    Isokinetic force (torque)

    Knee strength of the strongest leg was measured in a CYBEX 6000 device (Lumex Inc., Ronkonkoma, NY) at baseline and after 12 wk. The subjects sat leaning against a backrest reclined 15° from vertical. They were stabilized, i.e. strapped, at the shoulder, waist, and distal portion of the thigh; and the rotational axis of the dynamometer was aligned with the lateral femoral epicondyle. The lower leg was attached to the load cell positioned proximal to the ankle. Maximal isokinetic concentric knee extension and flexion were measured at an angular velocity of 60°·sec-1, followed by an angular velocity of 180°·sec-1. The subjects were familiarized to the procedure by four warm-up trials, followed by six maximal trials at each velocity, to ensure that peak torque, which was used as a measure of the maximal force, occurred within the trial ( 32). Strong verbal reinforcement was used to achieve an optimal effort level. Data were always corrected for the effect of gravity on the shank, foot, and ankle pad.


    NMRI was performed at baseline and after 12 wk. 2D T1-weighted fast field echo (TR/TE, 500/14 ms; FOV180; matrix 512 x 512; slice thickness, 6 mm) MR images (Philips, Gyroscan ACS-NT 1.5 T, Best, Holland) were obtained at a level positioned two thirds proximal along an axis connecting a fix point at the tibial eminentia intercondylaris with a fix point at the femoral trochanter major. The left leg was always examined to avoid possible interference with hematomas originating from muscle biopsies. The rectus femoris, vastus lateralis, vastus intermedius, and vastus medialis muscles were identified; and their circumference and cross-sectional area (CSA) were determined. Total quadriceps CSA was calculated by adding the four individual areas together. An estimate of sc fat CSA was obtained by subtracting leg CSA within the muscle fascia from total leg CSA. NMRI was not performed in the group receiving only placebo.

    Training program

    The subjects in the two training groups performed three different lower-body exercises: leg press, seated knee extension, and seated knee flexion. Exercises were performed as 3–5 sets of 8–12 repetitions. From wk 6–12, the load equaled 8 RM (repetition maximum). Four different upper-body exercises were also performed: pull-down, chest press, abdominal crunch, and back extension. The upper-body exercises were performed as 1 set of 8–15 repetitions. Exercises, except back extensions and abdominal crunches, were performed in weight-loaded strength-training machines (Technogym, Gambettola, Italy). Training was performed 3 times per week, and the total duration of one training session was approximately 30 min. An investigator supervised each training session; 1 RM was determined at baseline and after 12 wk.

    Blood sampling

    Whole blood was sampled at baseline and after 12 wk, from a cubital vein, into sealed vials without any additives; allowed to clot for 15 min at room temperature; and centrifuged for 15 min at 4 C. The resulting serum was transferred to appropriate tubes and stored at -80 C until analysis for GH-related serum parameters. Sampling was performed in the morning, after an overnight fast, and 24 h after the last training session for the 12-wk sample.

    Analytical methods

    Biopsies Histochemistry analysis.
    Serial sections (10-µm) of the muscle biopsy samples were cut in a cryostat (-20 C), and routine ATPase histochemistry analysis was performed after preincubation at pH 4.37, 4.60, and 10.30 ( 33). Five different fiber types were defined (1, 1/2a, 2a, 2ax, and 2x) according to Staron et al. ( 34, 35), with the modification that fibers termed by Staron et al. as 1c and 2ac (2c) were pooled into one group termed: 1/2a. Cross-sections from baseline and 12-wk biopsies from the same subject were transferred to the same slide and processed for ATPase histochemistry simultaneously. Fibers determined as type 2 fibers, but showing an intermediate staining with pH 4.60 preincubation, were categorized as type 2ab fibers ( 34, 35). These type 2ab fibers covered a wide range, from fibers with only a light staining (i.e. fibers with predominately MHC IIA content) to fibers with a darker staining (i.e. fibers with predominantly MHC IIX content) ( 36); 246 ± 8 fibers were examined in each of the biopsies. Only truly horizontally cut fibers were used in the determination of fiber size. Thus, a restricted number of fibers (170 ± 8 fibers in each biopsy) were used for this analysis ( 36).

    Analysis of serial cryosections.
    The serial sections were visualized and analyzed using an Olympus Corp. BX40 microscope (Olympus Corp. Optical Co., Ltd, Tokyo, Japan), a Sanyo Hi-resolution Color CCD camera (Sanyo Co., Ltd., Osaka, Japan), and an 8-bit Matrox Meteor Framegrabber (Matrox Electronic Systems Ltd., Québec, Canada), combined with image-analyzing software (Tema, Scanbeam, Hadsund, Denmark) ( 36).

    MHC analysis.
    MHC analysis was performed on the muscle biopsies, using SDS-PAGE; 10–20 serial cross-sections (20 µm) were cut from each biopsy. Cross-sections for MHC analysis were cut from the biopsies and were placed in 100–200 µl lysing buffer and heated for 3 min at 90 C ( 37); 5–20 µl of the myosin-containing samples were loaded on a SDS-PAGE gel containing 6% polyacrylamide and 30% glycerol. Gels were run at 70 V for 42 h in 4 C. Subsequently, the gels were Coomassie-stained, and MHC isoform content was determined with a densitometric system (Cream 1-D, Kem-En-Tec Aps, Copenhagen, Denmark) ( 36).

    Serum Total IGF-I was determined by RIA as previously described ( 38). Briefly, serum was extracted by acid-ethanol and was cryoprecipitated before analysis, to remove interfering IGF binding proteins (IGFBPs). Inter- and intraassay coefficients of variation were less than 9% and 6%, respectively. Details regarding determination of total IGF-I have been presented previously.

    IGF-II was determined by an immunoradiometric assay (Diagnostic Systems Laboratories, Inc., Webster, TX). Briefly, this assay is a noncompetitive assay in which the analyte is sandwiched between two antibodies. Samples were pretreated (1:1000) with acid-ethanol extraction to separate IGF-II from its binding proteins before measurement. Inter- and intraassay coefficients of variation were 6.3–10.4% and 4.2–7.2%, respectively ( 39).

    IGFBP-3 was determined by an RIA as previously described ( 40). Reagents for the assay were obtained from Mediagnost GmbH (Tübingen, Germany). The sensitivity was 0.29 µg·liter-1 (defined as 3 SD from the mean of the zero standard). Inter- and intraassay coefficients of variation were 10.7% and 2.4% (at bound-to-free ratios of 0.4–0.5), respectively. Details regarding determination of IGFBP-3 have been presented previously ( 41).

    Acid-labile subunit (ALS) was determined by a commercially available ELISA (Diagnostic Systems Laboratories, Inc.) ( 42). Standards ranged from 1.09–70 mg·liter-1. In our hands, interassay coefficients of variation (n = 22) were 20.4% (at 2.8 mg·liter-1) and 12.1% (at 17.6 mg·liter-1), respectively. Intraassay coefficients of variation (n = 20) were 8.6% (at 30.1 mg·liter-1) and 7.4% (at 8.4 mg·liter-1), respectively ( 43).

    Statistical analysis Data are presented as means ± SEM. Kruskal-Wallis test was used to detect significant differences in baseline characteristics between groups. Wilcoxon’s paired test was used to detect significant changes within groups. Mann-Whitney unpaired test was used to detect significant changes between groups. P < 0.05 (two-tailed) was considered significant.



    Thirty of 31 included subjects completed the study. One subject abandoned the study after 8 wk because of intolerable side effects attributable to GH administration (pitting leg edema). Baseline characteristics of the remaining 30 subjects, divided into RT + placebo (n = 8), RT + GH (n = 8), GH (n = 7), and placebo (n = 7), are presented in Table 1. There were no significant differences in baseline characteristics among the groups.

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    Table 1. Baseline characteristics of the 30 subjects completing the study

    GH administration
    Of the 15 subjects, who completed the study and received GH, 12 experienced side effects. In 10 of these subjects, a dose reduction was necessary. The expected final dose of 2.60 ± 0.05 IU·d-1 (10.6 ± 0.2 µg·kg-1·d-1) was thus reduced to 1.77 ± 0.18 IU·d-1 (7.2 ± 0.8 µg·kg-1·d-1) in the 2 GH groups. Side effects were mainly attributable to fluid retention (varying degrees of pitting leg edema, n = 10; carpal tunnel syndrome, n = 1; so-called triggerfingers, n = 1; transient atrial fibrillation, n = 1; weight gain, n = 1). Of the 15 subjects who completed the study and received placebo, 4 experienced side effects that necessitated a dose reduction. The expected final placebo dose of 2.60 ± 0.07 IU·d-1 (11.1 ± 0.2 µg· kg-1·d-1) was therefore reduced to 2.47 ± 0.08 IU·d-1 (10.6 ± 0.3 µg·kg-1·d-1) in the 2 placebo groups. Side effects were: mild leg edema (n = 2), headache (n = 1), and weight gain (n = 1). The difference in the proportion of side effects between the GH groups and the placebo groups was statistically significant (P = 0.009, Fisher’s exact test); and the final GH dose was significantly lower in the GH groups, compared with the final placebo dose in the placebo groups (P < 0.0025, Mann-Whitney).

    GH-related serum parameters

    The groups did not differ, with respect to serum IGF-I, IGF-II, IGFBP-3, or ALS at baseline (Table 2). In the two groups receiving GH, the three serum markers IGF-I, IGFBP-3, and ALS increased significantly from baseline to 12 wk, whereas IGF-II almost tended to increase (RT + GH, P < 0.054; GH, P < 0.078) (Table 2). No changes were observed in the two placebo groups from baseline to 12 wk (Table 2).

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    Table 2. GH-related serum markers

    There were no differences in body weight, FM (absolute and relative), FFM, or BMC between groups at baseline (Fig. 1). Body weight did not change in either group from baseline to 12 wk (Fig. 1A). RT + placebo and placebo alone did not cause any changes in body composition. However, RT + GH and GH alone decreased total FM (RT+GH, 3.16 ± 1.00 kg, P < 0.0078; GH, 2.27 ± 0.54 kg, P < 0.0156) and increased FFM (RT+GH, 2.52 ± 0.54 kg, P < 0.0078; GH, 2.46 ± 0.51 kg, P < 0.0156) to a similar extent, whereas BMC was unchanged in both groups (both P > 0.5) (Fig. 1). Regional body composition analysis showed that fat percentage was reduced in all three body compartments (arm, leg, trunk) in the RT + GH group and in two body compartments (leg and trunk) in the GH group (Fig. 2). Similarly, FFM percentage was increased in all three body compartments in the RT + GH group and in two body compartments (leg and trunk) in the group receiving only GH (Fig. 2).

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    Figure 1. A, Body weight; B, FM; C, FFM; D, BMC (all at baseline and after 12 wk). Bars and error bars represent mean values and SEM, respectively. *, Significant change within a group. See Results for further details.

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    Figure 2. Changes in total and regional FM and FFM as a result of the interventions. Changes calculated in percent from values of FM and FFM (measured in percent). Bars and error bars represent mean values and SEM, respectively. *, Significant change within a group.

    There were no differences in quadriceps CSA or sc femoral CSA between the groups at baseline (quadriceps CSA, P > 0.69; femoral sc CSA, P > 0.81). Quadriceps CSA increased significantly in the RT + placebo and in the RT + GH groups (RT + placebo, 6.3 ± 2.5%, P < 0.05; RT + GH, 10.4 ± 2.7, P < 0.0156), from baseline to 12 wk, but did not change in the group receiving only GH (P > 0.81) (Fig. 3). There was no difference in the magnitude of the increase in CSA between the two training groups (P < 0.16). Sc femoral CSA decreased significantly from baseline to 12 wk in the group receiving only GH (5.2 ± 1.9%, P < 0.0156), tended to decrease in the RT + GH group (6.3 ± 3.0%, P < 0.0781), and was unchanged in the RT + placebo group (0.6 ± 2.1%, P > 0.98) (Fig. 3).

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    Figure 3. CSA determined by NMRI. A, Quadriceps CSA at baseline and after 12 wk; B, change in quadriceps CSA from baseline to 12 wk, in percent; C, sc thigh CSA at baseline and after 12 wk; D, change in sc thigh CSA from baseline to 12 wk, in percent. Bars and error bars represent mean values and SEM, respectively. *, Significant change within a group; (*), P < 0.08).

    Isokinetic torque, 1 RM, and leg extensor power
    No differences in isokinetic quadriceps torque or leg extensor power were detected between the groups at baseline. Isokinetic quadriceps torque increased significantly and equally, by approximately 18–20% at both 60 and 180°·sec-1, in the two training groups from baseline to 12 wk but remained unchanged in the two nontraining groups (Fig. 4); 1 RM was only performed in the two training groups and increased significantly and equally, by approximately 65%, in both groups. Leg extensor power, measured in the Nottingham Power Rig, increased from baseline to 12 wk in the RT + placebo group (15 ± 3%, P < 0.0078) but did not change in any of the other three groups (Fig. 4).

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    Figure 4. Isokinetic quadriceps torques at A (60°·sec-1) and B (180°·sec-1). C, Quadriceps leg power; D, 1 RM leg extension. Measurements performed at baseline and after 12 wk. Bars and error bars represent mean values and SEM, respectively. *, Significant change within a group. See Results for further details.

    Fiber types
    There were no differences in fiber type composition among the three groups at baseline [type 1, P > 0.34 (Kruskal-Wallis); type 1/2a, P > 0.14; type 2a, P > 0.34; type 2a/2x, P > 0.46; type 2x, P > 0.84] (Fig. 5). No significant changes in fiber type composition were observed in the RT + placebo group from baseline to 12 wk. However, there was a tendency toward a decrease in type 1 fibers from 62.9 ± 6.3% to 52.6 ± 4.7% (P < 0.148), a tendency toward an increase in type 2a fibers from 24.4 ± 4.9% to 34.0 ± 5.6% (P < 0.109), and a tendency toward an increase in type 2a/2x fibers from 2.9 ± 1.2% to 4.9 ± 1.3% (P < 0.148), whereas type 2x fibers were unchanged [8.7 ± 3.1% (baseline) vs. 7.7 ± 3.5%, P > 0.84] (Fig. 5A). The same pattern was observed in the RT + GH group, where type 1 fibers tended to decrease from 61.4 ± 6.7% to 47.2 ± 4.0% (P < 0.109), type 2a fibers increased significantly from 24.2 + 5.5% to 35.4 + 5.5% (P < 0.0313), type 2a/2x increased significantly from 3.2 ± 1.2% to 11.0 ± 2.7% (P < 0.0156), and type 2x fibers were unchanged [9.8 ± 3.2% (baseline) vs. 5.0 ± 1.2%, P < 0.22] (Fig. 5B). In the group receiving only GH, a different pattern was observed, with a tendency for a decrease in type 2a fibers from 34.0 ± 5.5% to 22.4 ± 1.9% (P < 0.078) and a tendency for an increase in type 2x fibers from 7.5 ± 2.7% to 20.0 ± 2.6% (P < 0.078) (Fig. 5C).

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    Figure 5. Fiber type and MHC composition in quadriceps muscle biopsies obtained at baseline and after 12 wk. Bars and error bars represent mean and SEM, respectively. *, Significant change within a group. See Results for further details.

    Fiber size
    There were no differences in type 1 and type 2 fiber size among the three groups at baseline (type 1, P > 0.54, Kruskal-Wallis; type 2, P > 0.59). No significant changes were observed in type 1 and type 2 fiber size in any of the groups from baseline to 12 wk [RT + placebo, type 1, from 4521 ± 451 (baseline) to 4618 ± 364 (12 wk), P > 0.64; RT + placebo, type 2, from 3832 ± 418 to 4262 ± 530, P > 0.19; RT + GH, type 1, from 5066 ± 383 to 5172 ± 301, P > 0.46; RT + GH, type 2, from 4070 ± 234 to 4380 ± 291, P > 0.37; GH alone, type 1, from 4668 ± 492 to 4183 ± 304, P > 0.10; GH alone, type 2, from 4050 ± 241 to 4143 ± 200, P > 0.81] (all areas in µ·m-2). Similarly, no significant changes in fiber size from baseline to 12 wk were detected when the fibers were further divided into type 1, type 1/2a, type 2a, type 2a/2x, and type 2x (data not given). When pooling data from the two training groups, there was still no significant change in type 1 fiber size [from 4775 ± 298 (baseline) to 4877 ± 243 (12 wk), P > 0.42]; whereas the increase in type 2 fiber size almost reached significance (from 3943 ± 242 to 4317 ± 304, P < 0.064).

    MHC composition

    There were no differences in MHC composition among the three groups at baseline [MHC 1,P > 0.60 (Kruskal-Wallis); MHC 2A, P > 0.47; MHC 2x, P > 0.28] (Fig. 5). MHC composition did not change from baseline to 12 wk in the RT + placebo group (Fig. 5A). In the RT + GH group, MHC 1 decreased from 67.3 ± 5.7% to 53.7 ± 4.0% (P < 0.0234), MHC 2A increased from 26.2 ± 4.7% to 43.4 ± 3.7% (P < 0.0156), and MHC 2x decreased from 6.5 ± 1.9% to 2.9 ± 0.8% (P < 0.0469) (Fig. 5B). In the group receiving only GH, MHC 1 and MHC 2A composition did not change; whereas MHC 2x increased substantially and significantly, from 2.8 ± 1.2% to 11.1 ± 2.3% from baseline to 12 wk (P < 0.0156) (Fig. 5C).


    In the present study, we found no effect of 12-wk GH administration alone on isokinetic muscle strength or muscle power in healthy elderly men (Fig. 4, A–C). To our knowledge, the isolated effects of GH administration on muscle strength in healthy elderly humans has only been investigated in two previous studies, and they both showed that GH administration alone does not increase muscle strength in either elderly men (26) or women (27). Thus, our findings support the existing evidence. Even though FFM increased significantly with GH administration alone, it is impossible, from DEXA measurements, to obtain information about the various components that constitute the increase in FFM (44). Obviously, this is a major issue in trials investigating effects of GH administration on body composition and, in particular, on muscle mass, because GH is known to cause water retention (9). However, GH administration alone did not increase quadriceps muscle CSA determined by NMRI (Fig. 4) or induce fiber hypertrophy determined from quadriceps muscle biopsies. These findings further support that GH administration alone has little, if any, effect on skeletal muscle hypertrophy and strength in healthy elderly men.

    When GH administration was combined with RT, no further improvements in muscle strength were observed in the present study. In addition, both RT + placebo and RT + GH caused a significant, but similar, increase in muscle CSA, determined by NMRI (Fig. 4), whereas no effect was detected on muscle fiber sizes in either group. These findings support previous investigations in healthy elderly (17, 19) and young men (21) as well as in young power athletes (18, 45) but are in contrast to the findings by Welle et al. (20), who found that GH administration actually augmented training-induced strength in healthy elderly men. The reason for the conflicting results obtained by Welle et al. vs. Yarasheski et al. and Taaffe et al. is not immediately intelligible. Obviously, it cannot be excluded that GH administration may have resulted in small increments in muscle strength that escaped detection by the methods we used. Likewise, it cannot be excluded that elite athletes, in whom very small increases in performance result in dramatic improvements in ranking, may benefit from additional GH administration, although this may be difficult to substantiate scientifically. However, from the present study and from the previously published studies, we conclude that elderly men benefit substantially from RT, but additional GH administration does not further improve the gains in muscle hypertrophy and strength.

    Several (23, 24, 46), but not all (16, 47), studies investigating GH replacement therapy in GH-deficient adult patients have demonstrated small, but significant, increases in muscle strength. Although elderly are sometimes referred to as GH-deficient, this term may not be appropriate, because GH deficiency involves a heterogeneous group of patients covering both a wide age span and a wide range of hormonal disorders requiring several hormones for replacement therapy (sex steroids, corticosteroids, thyroid hormones, and others). It is therefore easy to imagine potential confounders in studies involving GHD patients, and results obtained in GHD patients are thus difficult to compare with results obtained in healthy elderly subjects.

    GH administration alone resulted in a dramatic increase in MHC 2X composition, paralleled by a similar increase in type 2x fibers, which almost reached statistical significance (Fig. 5C). It has been suggested that, with increasing age, there is a trend toward a shift in muscle MHC composition from 2x to 2A and 1 (48). It may thus be hypothesized that GH, by rejuvenating systemic IGF-I levels, may shift MHC composition to a more youthful profile in elderly people. However, in terms of muscle functionality, these changes in muscle MHC composition are not likely to be revealed by the muscle tests performed in the present study (Fig. 4). It would have been more appropriate to measure changes in the rate of force development. To our knowledge, there are no published data on the effect of GH administration on MHC composition in healthy humans. Several animal studies suggest that GH may influence fiber composition, but the results are far from uniform. In one study, GH administration to normal rats was found to selectively induce type II fiber hypertrophy (49). It is known that muscle fibers express IGF-I receptors (50), and current evidence suggests that muscle fibers also express GH receptors (51). However, the potential signaling pathways for the observed effect of isolated GH administration in the present study, either directly or indirectly through the actions of IGF-I, remain to be elucidated.

    Skeletal muscle MHC or fiber type composition did not change with RT alone, whereas a decrease in MHC 1 and an increase in MHC 2A, accompanied by similar changes in fiber type composition, were observed when RT was combined with GH (Fig. 5, A and B). The latter findings are consistent with changes reported in previous RT studies in elderly (48) and suggest that GH administration combined with RT does not change the direction of MHC changes that occur with RT alone. However, a recent study demonstrated increased levels of MHC 1 mRNA and decreased levels of MHC 2A and 2x mRNA with RT in elderly subjects (52). Because we demonstrated either no change (RT alone) or even opposite changes in MHC composition at the protein level, it may be that the apparent increase in MHC 1 mRNA and concomitant decreases in MHC 2A and 2x mRNA are not propagated to the translational or posttranslational levels. Alternatively, a change in the protein degradation among the different MHC isoforms may counteract the changes in mRNA expression. Currently, the training stimulus was able to completely overrule the effects of isolated GH administration on MHC changes, and these findings support that mechanical stretch and systemic GH (or IGF-I) act through different signaling pathways. MHC 2x fibers are known to possess low insulin sensitivity (53), and a shift in MHC composition toward higher percentage of MHC 2x may play a role in the well-known effect of GH administration to decrease insulin sensitivity.

    GH administration caused substantial changes in body composition, determined by DEXA scanning, with increased FFM and decreased FM after 12 wk (Fig. 1). These findings confirm previous observations (15, 26) and support the widely accepted view that GH plays a major role in determining body composition. The decrease in FM was also evidenced by the decrease in sc thigh CSA, measured by NMRI, in the two groups receiving GH (Fig. 3D). Although GH has a major impact on bone growth, no change in BMC was observed in any of the GH groups. However, the study period may very well be too short to make definitive statements about changes in BMC.

    Currently, 12 of the 15 subjects receiving GH and completing the study experienced side effects. A high incidence of side effects has been reported in several papers; but, in retrospect, we obviously targeted a too-high GH dose, and further dose reductions are necessary in future studies involving healthy elderly men.

    In conclusion, the present study confirms that GH administration alone does not increase muscle strength or hypertrophy in healthy elderly men. Furthermore, healthy elderly men adapt beneficially to a 12-wk RT program, with substantial increases in muscle mass and muscle size. However, GH administration does not further augment these training-induced adaptations. GH administration alone seems to increase muscle MHC 2x, possibly through rejuvenating systemic IGF-I levels, whereas this response is completely overruled when RT is combined with GH. The present study does not support that GH therapy either alone or in combination with RT should be used to augment muscle strength and/or hypertrophy in elderly men.
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  17. Quote Originally Posted by TooL
    In regards to hormones and exercise selection. Can you not get the same response from doing leg press?
    You get the same response with any rigorous exercise, HIIT training included. But the point is that in the big picture, it doesn't have much of an additive effect at all.
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  18. exactly. or at least that effect being anabolic is FAR from proven, is speculative at best, and there is a lot of evidence to the contrary.

    i have long found it typical that squatting is somewhat of a religion with some people. now, don't get me wrong. i like religion. but what i mean is that it is taken as a priori The Truth (tm) and the standards of evidence just cease to exist to those who worship the God of Sqwhat (tm)

    the squat is - FOR ATHLETES - a phenomenal or even arguably a nearly necessary exercise. iirc, it was roman who said it teaches the "Fundamental position in sport" and you will not find an OLer coach who does not use it successfully (although some have argued for stepups but i digress)

    but for Muscle Hypertrophy?

    the muscles only know tension. they do not know exercises. it's that simple. i love to squat, and i have done so as much as 5 times a week. however, it is hardly the magic pill that IA et al claim it to be. it is neither sufficient nor necessary for lower body growth, or potentiation of upper body growth in and of itself (w/o proper tension etc. ie loading)

    load the leg muscles with sufficient tension and they will grow


    end of story.

    squats are arguably the best way to do this, but hardly the magic pill

  19. About 5 years ago, I injured may lower back and every time I have tried to squat I pay for it for about a week. So I gave up on squats and deadlifts. I have made pretty impressive gains from the leg press, more so then when I did squats. Of course, I was younger then and other factors exist, but I agree with jjjd that you still make solid lower body gains without squats.

  20. Quote Originally Posted by jjjd
    exactly. or at least that effect being anabolic is FAR from proven, is speculative at best, and there is a lot of evidence to the contrary.

    i have long found it typical that squatting is somewhat of a religion with some people. now, don't get me wrong. i like religion. but what i mean is that it is taken as a priori The Truth (tm) and the standards of evidence just cease to exist to those who worship the God of Sqwhat (tm)

    the squat is - FOR ATHLETES - a phenomenal or even arguably a nearly necessary exercise. iirc, it was roman who said it teaches the "Fundamental position in sport" and you will not find an OLer coach who does not use it successfully (although some have argued for stepups but i digress)

    but for Muscle Hypertrophy?

    the muscles only know tension. they do not know exercises. it's that simple. i love to squat, and i have done so as much as 5 times a week. however, it is hardly the magic pill that IA et al claim it to be. it is neither sufficient nor necessary for lower body growth, or potentiation of upper body growth in and of itself (w/o proper tension etc. ie loading)

    load the leg muscles with sufficient tension and they will grow


    end of story.

    squats are arguably the best way to do this, but hardly the magic pill
    Bascially this is the conclusion I have come to. We know the goals (i.e muscle hypertrophy and/or neural adaptation) and those do not change. Squats seem to be the best way to get there, but one doesn't have to use them nor do they seem to provide anything that couldn't be accomplished anyway, it just may seem less efficient to do so another way.

  21. I think body type plays a big role as well. Someone with a long torso and short legs might not get as much out of a squat as they do leg press. Leverage could cause the squat to stress the lower back a little to much. In that case the lifter would stop the exercise short of enough stimulus to cause the legs to grow.

  22. Thats strange.... For my frame I've got a long torso and short legs 5'7" tall 27" inseam, and I get a LOT out of squats and have much better "natural" form than my buddy who has the reverse problem.

    -Saving random peoples' nuts, one pair at at time... PCT info:
    -Are you really ready for a cycle? Read this link and be honest:
    *I am not a medical expert, my opinions are not professional, and I strongly suggest doing research of your own.*

  23. I think it also depends on where your flexibility is. With all the joints that are involved one person of the same body types ROM can be much different then anothers.

  24. I feel that no.. squats aren't the only way, but for anyone that can do them properly, they are one of the easiest ways to really hit your legs HARD, without having to do a bunch of differeint exercises.

    -Saving random peoples' nuts, one pair at at time... PCT info:
    -Are you really ready for a cycle? Read this link and be honest:
    *I am not a medical expert, my opinions are not professional, and I strongly suggest doing research of your own.*

  25. of course squats arent completely necessary for growth, this is really a meaningless arguement. Are they the best for growth? I would say YES


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